Rh2 is a ginsenoside extracted from ginseng that has drawn attention in a few laboratories in Asian countries because of its potential tumor-inhibitory effect. In the present study, we tested Rh2 on many tumor-cell lines for its effects on cell proliferation, induction of apoptosis, and potential interaction with conventional chemotherapy agents. Our results showed that Rh2 inhibited cell growth by G1 arrest at low concentrations and induced apoptosis at high concentrations in a variety of tumor-cell lines, possibly through activation of caspases. The growth arrest and apoptosis may be mediated by 2 separate mechanisms. Apoptosis is not dependent on expression of the wild-type p53 nor the caspase 3. In addition, the apoptosis induced by Rh2 was mediated through glucocorticoid receptors. Most interestingly, Rh2 can act either additively or synergistically with chemotherapy drugs on cancer cells. Particularly, it hypersensitized multidrug-resistant breast cancer cells to paclitaxel. These results suggest that Rh2 possesses strong tumor-inhibiting properties, and potentially can be used in treatments for multidrug-resistant cancers, especially when it is used in combination with conventional chemotherapy agents.

In this piece of work we focused our attention on the peroxidation step and alongside considered hydroperoxides as probes for the overall oxidative process. This technique of oxygen uptake actually monitors the amount of oxygen consumed during polymer degradation. Our present work aimed to investigate this technique to evaluate the oxygen uptake during in situ photoirradiation, under controlled atmosphere. Our experimental results clearly elucidate that the oxygen consumption data accounts for a very early stage of aging during the photo‐oxidation of polymers and provides us with an accurate and sensitive diagnosis about the formation of hydroperoxides. A straight‐line relationship was exhibited under our experimental conditions while observing a relation between oxygen pressure drop and hydroperoxide content in the polymer. This correlation was dependent upon the nature of polymer and of course on the aging conditions (temperature, irradiation, oxidative atmosphere). The impact of environmental atmosphere on aging was particularly kept in mind. To conclude, we emphasized that oxygen uptake is a promisingly powerful tool to identify the impact of the overall environmental parameters on the polymer photoaging. An important implication was on the understanding of atmospheric factors (including pollutants such as O3, NOx, etc.), which is usually given minor importance, on the degradation of polymer upon outdoor weathering. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006

Oncolytic virotherapy is a promising new tool for cancer treatment, but direct lytic destruction of tumor cells is not sufficient and must be accompanied by strong immune activation to elicit anti-tumor immunity. We report here the creation of a novel replication-competent recombinant oncolytic herpes simplex virus type 1 (VG161) that carries genes coding for IL-12, IL-15, and IL-15 receptor alpha subunit, along with a peptide fusion protein capable of disrupting PD-1/PD-L1 interactions. The VG161 virus replicates efficiently and exhibits robust cytotoxicity in multiple tumor cell lines. Moreover, the encoded cytokines and the PD-L1 blocking peptide work cooperatively to boost immune cell function. In vivo testing in syngeneic CT26 and A20 tumor models reveals superior efficacy when compared to a backbone virus that does not express exogenous genes. Intratumoral injection of VG161 induces abscopal responses in non-injected distal tumors and grants resistance to tumor re-challenge. The robust anti-tumor effect of VG161 is associated with T cell and NK cell tumor infiltration, expression of Th1 associated genes in the injection site, and increased frequency of splenic tumor-specific T cells. VG161 also displayed a superb safety profile in GLP acute and repeated injection toxicity studies performed using cynomolgus monkeys. Overall, we demonstrate that VG161 can induce robust oncolysis and stimulate a robust anti-tumor immune response without sacrificing safety.

20S-Protopanaxadiol (1) is an aglycon metabolic derivative of the protopanaxadiol-type ginseng saponins. In the present study, 1 was used to induce cytotoxicity for two human glioma cell lines, SF188 and U87MG. For the SF188 cells, 1 activated caspases-3, -8, -7, and -9 within 3 h and induced rapid apoptosis, which could be partially inhibited by a general caspase blocker and completely abolished when the caspase blocker was used in combination with an antioxidant. Compound 1 also induced cell death in U87MG cells but did not activate any caspases in these cells. Monodansylcadaverine staining showed that 1 induced dramatic autophagy in both cell lines. Elevated levels of superoxide anion in both cells and reduced levels of phosphorylated Akt in U87MG cells were also demonstrated. These results showed that 20S-protopanaxadiol (1) induces different forms of programmed cell death, including both typical apoptosis and autophagy through both caspase-dependent and -independent mechanisms.

Herpes simplex virus types 1 and 2 (HSV-1, -2) infect and also establish latency in neurons. In the present study, the authors investigated the influence of neuronal activity on the replication of HSV-1. The results showed that the sodium channel blocker tetrodotoxin (TTX) and the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) could significantly increase viral replication in primary neuronal cultures, by two- to fourfold. In contrast, KCl reduced viral production by at least 80% in the same cultures. Inhibitors of GABA(A) receptors completely abolished the effects of GABA. Intravitreously injected TTX in a mouse corneal scarification model enhanced the viral titers > 10-fold in both the trigeminal ganglia and the brain. At 2 h post infection, both TTX and GABA significantly up-regulated the levels of transcription for the viral immediate early (IE) genes ICP0, ICP4, and ICP27, as revealed by real time PCR. These results indicate that the neuronal excitation status may dictate the efficiency of HSV-1 viral replication, probably by regulating the levels of viral IE gene expression. These are the first findings connecting neuronal activity to the molecular mechanisms of HSV replication in the nervous system, which may significantly influence our view of herpesvirus infection and latency.